Evidence that angiotensin‐(1–7) is an intermediate of gonadotrophin‐induced oocyte maturation in the rat preovulatory follicle

Abstract

Several studies have shown the presence of components of the renin-angiotensin system in mammalian ovaries and their involvement in ovarian physiology. We have previously shown the presence of angiotensin-(1-7) [Ang-(1-7)], an important biologically active component of the renin-angiotensin system, and its receptor, Mas, in rat, rabbit and human ovaries. We have also shown the involvement of Ang-(1-7) in the rabbit ovulatory process in vitro. In the present study, we observed that Ang-(1-7) stimulated the resumption of meiosis in oocytes of rat preovulatory follicles, reaching more than 30% of oocytes with germinal vesicle breakdown. The specific antagonist of the Mas receptor, A-779, inhibited the germinal vesicle breakdown induced by Ang-(1-7) and reduced the oocyte maturation stimulated by luteinizing hormone (LH). Immunohistochemistry showed that LH increased both Ang-(1-7) and angiotensin-converting enzyme 2 (ACE2) staining in preovulatory follicles. The effect of gonadotrophins on mRNA expression of Mas and ACE2 in ovaries of immature equine chorionic gonadotrophin-primed rats was analysed by real-time PCR after 6 h of human chorionic gonadotrophin (hCG) injection, which exhibits LH-like effects. After hCG treatment, ACE2 mRNA expression was higher in the ovaries of treated rats than in the ovaries of control rats, whereas Mas mRNA levels were unchanged. A-779 changed the steroidogenesis stimulated by LH. An increased testosterone concentration and decreased progesterone levels were measured in the follicle medium. In conclusion, our results suggest that LH upregulates the ACE2-Ang-(1-7)-Mas axis and that Ang-(1-7) promotes meiotic resumption, possibly as a gonadotrophin intermediate.

International Union of Basic and Clinical Pharmacology. XCIX. Angiotensin Receptors: Interpreters of Pathophysiological Angiotensinergic Stimuli

“…Consistent with a regulatory role of MAS in ovary, the MAS antagonist A-779 was shown to prevent breakdown of germinal vesicle and reduced oocyte maturation induced by Ang(1-7) (Honorato- Sampaio et al, 2012). Expression of MAS in uterus and placenta is thought to be relevant to diseases such as preeclampsia (Velloso et al, 2007).…”

Sex-Specific SARS-CoV-2 Mortality: Among Hormone-Modulated ACE2 Expression, Risk of Venous Thromboembolism and Hypovitaminosis D

“…Male mice fed with a high-fat diet showed a decreased ACE2 expression in the kidney, resulting in reduced angiotensin (1-7) and increased angiotensin (1-8) levels. This caused blood hypertension that was reversed by the administration of losartan [14]. The same authors had previously shown a low expression of ACE2 in the adipose tissue of male mice [15].…”

“…ACE2 has also been described in ovarian granulosa cells and its expression increases with a rise in luteinizing hormone (LH). Indeed, stimulation with human chorionic gonadotropic (hCG) improves the ACE2-angiotensin (1-7)-Mas system [14]. This may represent a compensatory mechanism that could be useful for avoiding an increase in blood pressure in postmenopausal women [15].…”

The ACE2/Angiotensin-(1–7)/MAS Axis of the Renin-Angiotensin System: Focus on Angiotensin-(1–7)

“…The presence of ANG-(1-7) in the ovary was initially described by Costa et al in 2003 (100). These authors also were the first to suggest an involvement of the ANG-(1-7) peptide in pre-and postovulatory events, demonstrating higher levels of ANG-(1-7) in the proestrus and estrus as well as in equine chorionic gonadotropin (eCG)-treated rats (254). Later, the same group demonstrated that the ACE2/ ANG-(1-7)/MAS axis is fully expressed in rat ovaries (419) and in all stages of follicular development in humans (436).…”